USAG1 (uterine sensitization‑associated gene 1), also called WISE (Wnt modulator in surface ectoderm) or Ectodin, gene name SOSTDC1, is a secreted, monomeric 26 ‑ 32 kDa glycoprotein of the sclerostin family of BMP antagonists. USAG1 is proposed to coordinate BMP, Wnt, FGF and SHH signals that regulate apoptosis during tooth development. Deletion of USAG1 results in mice with supernumerary teeth, while concurrent decreased expression of LRP5 and LRP6 restores normal tooth configurations. USAG1-/- mice show decreased susceptibility to kidney injury which is reversed by administration of a neutralizing antibody to BMP7. In a mouse model of Alport syndrome, deletion of USAG1 alternates disease progression. These results support a proposed USAG1/WISE antagonism of BMP and Wnt signaling pathways in kidney and tooth development. USAG1 expression by uterine luminal epithelium is also associated with the timing and positioning of blastocyst implantation.
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